Adenoviruses and coxsackieviruses are common human pathogens. Adenoviruses, non-enveloped DNA viruses, are a major cause of respiratory and gastrointestinal infections (Horwitz, In Virology, 3rd edition: 2149-2171 1996), as well as infections of the heart (Martin et al., Circulation, 90: 330-339 1994). In addition to their importance as disease agents, adenoviruses have been adapted for use as vectors for vaccination and gene therapy (Kremer and Perricaudet, British Medical Bulletin, 51: 31-44, 1995). Coxsackie B viruses, non-enveloped RNA viruses belonging to the picornavirus family, cause non-specific febrile illnesses and meningoencephalitis (Melnick, In Virology, 3rd edition: 655-712, 1996), and are the viruses most frequently identified in acute infections of the heart (Grist and Reid, In Viral Infection of the Heart, 23-31, 1993; Savoia and Oxman, In Principles and Practice of Infectious Diseases, 4th edition, 799-813, 1995). Coxsackie B viruses are also implicated in acute pancreatitis (Imrie et al., Gut, 18: 53-56, 1977) and as triggering-agents in childhood-onset diabetes (Yoon et al., New England Journal of Medicine, 300: 1173-1179, 1979; Clements et al., Lancet, 346: 221-223, 1995).
Viruses initiate infection by attaching to cell surface receptors, and tissue-specific expression of receptor molecules is an important determinant of virus tropism. Adenovirus attachment to cells is mediated by elongated fibers projecting from each of the 12 vertices of the icosahedral viral capsid. Isolated soluble fibers bind cells with high affinity, and block virus attachment and infection, demonstrating that fiber attachment to a cell surface receptor is a critical event in infection (Philipson et al., J. Virology, 49: 635-640, 1968; Defer et al., J. Virology, 64: 3661-3673, 1990; Wickham et al., Cell, 73: 309-319, 1993). Human adenoviruses are grouped on the basis of their ability to agglutinate erythrocytes. Competition experiments suggest that adenoviruses 2 and 5 (members of agglutination group C) share a common cellular receptor (Philipson et al., J. Virology, 49: 635-640, 1968; Defer et al., J. Virology, 64: 3661-3673, 1990), distinct from the receptor used by group B viruses such as adenovirus 3 (Defer et al., J. Virology, 64: 3661-3673, 1990; Stevenson et al., J. Virology, 69: 2850-2857, 1995) or 35. Although a number of cellular proteins associate with adenovirus on affinity columns (Hennache and Boulanger, Biochemical Journal, 166: 237-247, 1977; Svensson et al., J. Virology, 38: 70-81, 1981) or in virus overlay blot assays (Defer et al., J. Virology, 64: 3661-3673, 1990), the cellular molecules responsible for fiber-mediated adenovirus attachment have not been identified.
Twenty years ago, it was demonstrated that adenovirus 2 or its fibers compete with coxsackievirus B3 for a cell surface attachment site, suggesting that these unrelated viruses share a receptor protein (Lonberg-Holm et al., Nature, 259: 679-681, 1976). More recently, coxsackie B viruses have been shown to interact with at least two cell-surface proteins (Reagan et al., J. Virology, 49: 635-640, 1984), Decay accelerating factor (DAF, CD55) serves as an attachment receptor for some coxsackie B virus strains (Bergelson et al., J. Virology, 69: 1903-1906, 1995; Shafren et al., J. Virology, 69: 3873-3877, 1995). Expression of human DAF on rodent cells permits these strains to bind, but not to replicate, suggesting that additional factors may be required for infection.
A second 45-50 kD putative receptor molecule forms a detergent-stable complex with coxsackieviruses B3 and B4 (Mapoles et al., J. Virology, 55: 560-566, 1985; Hsu et al., In New Aspects of Positive-Strand RNA Viruses, 271-277, 1990). A monoclonal antibody raised against this complex is reported to protect cells from infection by all six coxsackie B serotypes (Hsu et al., J. Virology, 62: 1647-1652, 1988), consistent with the observation that all six serotypes compete for a single cell surface receptor (Crowell and Tomko, In Cellular Receptors for Animal Viruses, 75-99, 1994).